QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, December 6, 2006, 26(49):12672-12681; doi:10.1523/JNEUROSCI.0294-06.2006

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (8) Citing Articles via Google Scholar Google Scholar Articles by Liñares, D. Articles by Willenborg, D. O. Search for Related Content PubMed PubMed Citation Articles by Liñares, D. Articles by Willenborg, D. O.

 Previous Article  |  Next Article 

Neurobiology of Disease
Neuronal Nitric Oxide Synthase Plays a Key Role in CNS Demyelination

David Liñares,¹ Maaike Taconis,¹ Paula Maña,² Manuel Correcha,¹ Sue Fordham,¹ Maria Staykova,¹ and David O. Willenborg¹

¹Neurosciences Research Unit, Australian National University Medical School, Canberra Hospital, and ²The John Curtin School of Medical Research, Australia National University, Canberra, Australian Capital Territory 2601, Australia

Correspondence should be addressed to David Liñares, Neuroscience Research Unit, Australian National University Medical School, The Canberra Hospital, P.O. Box 11, Woden, Canberra, Australian Capital Territory 2606, Australia. Email: david.linares{at}anu.edu.au or Email: rosellon{at}usc.es

Nitric oxide (NO) is a small, short-lived molecule released from a variety of cells that is implicated in a multitude of biological processes. In pathological conditions, overproduction of NO may lead to the generation of highly reactive species, such as peroxynitrite and stable nitrosothiols, that may cause irreversible cell damage. Accordingly, several studies have suggested that NO may be involved in the pathogenesis of various neuroinflammatory/degenerative diseases. Increased concentrations of NO in the CNS in such cases are usually attributed to an increase in the inducible isoform of NO synthase (iNOS) usually produced by inflammatory cells. However, recent reports have suggested that the constitutive isoforms of NOS, neuronal (nNOS) and endothelial (eNOS), can also play a role. Here we examined the role that the constitutive isoforms of NOS might play in the cuprizone-induced model of demyelination/remyelination. Our results demonstrate that demyelination was greatly prevented in mice lacking nNOS. Protection was associated with a dramatic increase in mature oligodendrocyte survival and a decrease in apoptosis. Moreover, nNOS^–/– mice did not respond to cuprizone with the extensive recruitment of microglia/macrophages and astrocytes, which is a typical feature in wild-type mice. Although demyelinating less, nNOS^–/– mice exhibited a delay in remyelination. In eNOS^–/– mice, demyelination progressed to the same extent as in wild type, but they showed a slight delay in spontaneous remyelination. In conclusion, this study highlights the importance of considering the source of NO when assessing its role in neuroinflammation/degeneration and emphasizes the differing pathological effects driven by the different NOS isoforms.

Key words: cuprizone; nNOS; eNOS; demyelination; remyelination; oligodendrocytes

---

Received Sept. 21, 2005; revised Oct. 26, 2005; accepted Oct. 26, 2006.

Correspondence should be addressed to David Liñares, Neuroscience Research Unit, Australian National University Medical School, The Canberra Hospital, P.O. Box 11, Woden, Canberra, Australian Capital Territory 2606, Australia. Email: david.linares{at}anu.edu.au or Email: rosellon{at}usc.es

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help